This core provides specialized services required for all four projects of the PPG. These are best coordinated by a core to increase efficiencies of time and cost, promote scientific synergies, and maximally utilize dedicated highly specialized facilities. This program grant is a multidisciplinary investigation of in vivo and in vitro models of endosomal, autophagic, and lysosomal abnormalities in AD considered critical to AD pathogenesis. Neuropathological assessment and biochemical quantification of AD pathologies in these models is a major goal of the core. Other core functions are the maintenance of critical reagents (antibodies and cell lines) that are used in every project and must be maintained under rigorously controlled conditions to allow reliable comparisons of information across projects. The specific aims are: 1. To acquire, store and efficiently distribute well-characterized tissues (brain and fibroblasts) from cases of AD, FAD, Trisomy 21 and non-demented and non-AD neurological controls in a coordinated manner for studies in all four projects. 2. To perform electron microscopy and immunogold electron microscopy on cell and mouse models and human brain. 3. To perform ELISA measurements of Ab40 and Ab42 to quantify endogenous murine Ab and human Ab in AD brain, brains of mouse models, medium and lysates of fibroblasts and other cell models, and, when appropriate, to perform liquid chromatography-mass spectroscopy to identify Ab peptides and peptide cleavage sites on APP metabolites. 4. To provide specialized histological procedures and morphometric techniques as needed to characterize neurodegeneration and other AD pathologies as well as provide training on laser confocal microscopy and video-fluorescent microscopy. 5. To maintain and distribute polyclonal and monoclonal antibodies and generate additional polyclonal antibodies as necessary. 6. In years 08-10 of the PPG, to provide in vivo functional MRI analysis for selected animal models to characterize alterations in pathology longitudinally. The core serves all projects and is essential to their success.